The objective of this project is to study the development of and to identify the cause of corticomedullary intratubular nephrocalcinosis (NC) observed in female F344 rats fed NIH-31 or NIH-07 open formula diets. In early 1986 in an intramural study severe NC was observed histologically in the cortex of 42 and 56 day old control and treated female F344/Cr1BR rats which had been fed NIH-31 diet for 15 and 28 days respectively. Prior to 28 days of age they had access to a commercial rodent diet. Female F344 rats are recognized as being prone to NC; however, the lesions observed were more severe than had been seen previously. Analysis of the NIH-31 diet was consistent with the prescribed nutrient values, including Ca, P, Mg, and Vit. D. No estrogenic activity was demonstrated by bioassay. NC was observed in rats given NIH-31 and deionized or tap water. Parallel studies done in a second facility also revealed NC at 42 and 56 days of age. Two colonies of F344/N rats from the same supplier but maintained on NIH-31 from 2 different feed manufacturers were compared. Both colonies developed NC by 42 days of age. Kidneys from F344/N rats fed NIH-07 during long term studies in the National Toxicology Program were examined. Minimal evidence of NC was found in rats more than 20 weeks of age. A study of F344/N rats is underway to follow the progress of this lesion over a period of one year. Further, studies are being planned to examine the possible role of phytoestrogenic substances which may be present in certain feed stuffs depending on their origin and crop year.